Boronic ester bonding integrated dextran-based hydrogel patch for diabetic peripheral nerve injury treatment

Abstract

Peripheral nerve injury (PNI) is a common clinical complication of diabetes, however, lacks effective clinical treatment due to complex pathological microenvironment. Considering both biomimetic remodeling and pathological reversal, we proposed a boronic ester bonding integrated strategy to develop dextran-based hydrogel patch with dopamine methacrylate-conjugated exosomes (mExo) immobilization. Aldehyde/phenylboronic acid difunctional dextran was synthesized to establish hydrogel skeleton and provide self-adhesion and ROS/glucose modulation capacities for neuroprotection. Meanwhile, mExo as therapeutic factors were immobilized into hydrogels via boronic ester bonding and released in pathologic response to target mitochondrial dysfunction and achieve neurotherapy. Through in vitro assays, the composite hydrogel patch was shown to reduce oxidative stress by ROS scavenging, thereby protecting the mitochondrial morphological and functional homeostasis of healthy RSC96 cells. Indeed, the sustained released exosome conjugates regulated bioenergy metabolism and alleviated mitochondrial dysfunction in hyperglycemia damaged RSC96 cells by the up-regulated expression of E-cadherin and AMPK proteins. In vivo experiments proved that through correcting diabetic pathology and targeted treatment of damaged mitochondria, the hydrogel patch inhibited neuronal apoptosis and finally promoted axon regeneration, remyelination and motor function recovery after PNI in diabetic rats. The synergistic “two-pronged” strategy of biomimetic remodeling and pathological reversal opens a promising opportunity for non-invasive treatment of diabetic PNI.